tbuckley/cabot-search huggingface dataset:
PB2078: A RETROSPECTIVE ANALYSIS OF THE EFFICACY OF LOW-DOSE METRONOMIC CYCLOPHOSPHAMIDE FOR TREATMENT IN PATIENTS WITH LOW GRADE NON-HODGKIN LYMPHOMA
Authors: B. Han, B. J. Kim, H. Y. Kim, D. Y. Zang, H. J. Kim
Journal: HemaSphere (2022)

Background: Low-dose metronomic cyclophosphamide chemotherapy is an emerging strategy offering a potentially less toxic yet effective treatment modality. Aims: We evaluated the efficacy and safety of low-dose metronomic cyclophosphamide in patients with low grade non-Hodgkin lymphoma (NHL) by retrospectively reviewing the data. Methods: The patients received oral cyclophosphamide (50 mg per day) and/or oral methotrexate (2.5 mg twice weekly) until disease progression or unacceptable toxicity was noted. Results: Of the 36 patients, 17 (47.2%) were male, median age was 66.4 years (range, 37-91 years), and subtypes of NHL were mucosa associated lymphoid tissue lymphoma (55.6%), small lymphocytic lymphoma (13.9%), follicular lymphoma (11.1%), mantle cell lymphoma (8.3%), nodal marginal zone lymphoma (4.5%), splenic marginal zone lymphoma (2.8%), and lymphoplasmacytic lymphoma (2.8%). The stage I, II, III, IV were 38.9%, 13.9%, 11.1%, 36.1%, respectively and 55.6% of patients received this regimen as the first-line treatment, mainly due to frailty, refusal to standard chemotherapy. The overall best response rate (ORR) was 73.5% (12 complete responses, CRs and 13 partial responses, PRs), with 29.1 months of the median duration of response and the disease control rate was 88.2%. The median treatment duration was 8.8 months (range, 0.1-38.4 months); the median progression-free survival (PFS) was 43.5 months, and the median overall survival (OS) was not yet reached. Especially, the ORR in patients who were treated with metronomic cyclophosphamide as the first line treatment and as more than the second line treatment were 78.9% (10 CRs, 5 PRs) and 66.6% (2 CRs, 9 PRs), respectively. The median PFS were not reached in the first line cyclophosphamide treatment group and 26.5 months (range, 5.7-47.2 months) in the other group (p=0.110), and similarly, the median OS were not reached and 64.4 months (0-135.7 months) (p=0.058), respectively. The regimen was generally well tolerated, with small numbers of grade 3-4 toxicities; neutropenia (2%), anemia (3%), thrombocytopenia (3%), fatigue (4%), and anorexia (1%). Summary/Conclusion: We concluded that low-dose metronomic cyclophosphamide represents efficacious and well-tolerated treatment for low-grade NHL patients.
PB1764: THE CHARACTERISTICS, TREATMENT PATTERNS, AND SURVIVAL OF ADULT ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) TREATED BY GRAALL OR GRAAPH PROTOCOL
Authors: Y. Fakhfakh, F. Kammoun, I. Frikha, M. Charfi, M. Chaari, N. Louati, N. Abdeljalil, O. Kassar, F. Kallel, I. Ben Amor, L. Khalifa, M. Medhafar, S. Hadiji, H. Elleuch, H. Mnif, T. Ben Othman, M. Elloumi
Journal: HemaSphere (2022)

Background: The clinical features, treatments, and survivals of adult ALL patients are very different from the pediatric ALL patients. However, since the use of pediatric-like protocols for Philadephia (Ph) negative ALL (GRAALL), and treatments based on tyrosine kinase inhibitor (TKI) for Ph + ALL (GRAAPH), great improvements in adult ALL therapy have resulted. Aims: Our study aims to evaluate the characteristics, treatment patterns, as well as therapeutic results of ALL adult patients treated by GRAALL or GRAAPH protocol in a Tunisian center. Methods: Our study is retrospective about newly diagnosed ALL adult patients (>30 years old) treated between 2004 and 2020 at the hematology department of Hedi Chaker Hospital, Sfax, Tunisia, according to the GRAALL protocol for ph negative ALL, and the GRAAPH protocol (TKI containing treatment) for ph+ ALL. Imatinib was the first line TKI used. Allogenic hematopoietic stem cell transplantation (Allo-HSCT) was indicated for Phi+ and high-risk phi negative patients aged less than 50 years, and in complete remission. It was done in the national bone marrow transplant center. Results: A total of 70 patients were enrolled. Fifty-five patients were phi negative ALL treated with GRAALL protocol, and 15 were ph+ ALL and treated with GRAAPH protocol. We did not note any secondary ALL in our study. The clinical features, treatment patterns, and clinical outcomes are reported in Table 1. The realization of the A-HSCT was a predictive adverse prognostic factor for OS and PFS in both groups (p=0.015). Image:Summary/Conclusion: Our study is consistent with clinical trial findings of adult ALL reported in the literature, showing that compared with Phi negative patients, Phi + patients present more hyperleukocytosis forms and neurological involvement, and are more cortiocoresistant. However, they have higher complete remission rates and better survival due to the TKI- containing treatments. Moreover, despite the better therapeutic results in this group, our results are still lower than that reported in international studies, which incites us to a better involvement of A-HSCT, the only curative treatment for these patients.
Association of Children’s Hospital Status With Value for Common Surgical Conditions
Authors: Mehul V. Raval, Audra J. Reiter, Ian M. McCarthy
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Although children's hospitals (CH) provide a substantial proportion of highly specialized pediatric care in the United States, the value of CH compared with non–children's hospitals (NCH) for routine surgical procedures is unknown. <h3>Objective</h3> To examine the value of CH for routine surgical procedures by assessing clinical outcomes and payment data. <h3>Design, Setting, and Participants</h3> This retrospective cohort study examined pediatric patients undergoing 1 of 13 commonly performed surgical procedures between 2010 and 2015 with 90-day follow-up using administrative data from the Health Care Cost Institute. Data analysis was conducted from July 2019 to December 2021. <h3>Exposures</h3> The primary exposure was tier of CH status, defined using self-reported pediatric services, affiliation with pediatric focused programs, and validated based on proportion of pediatric admissions. <h3>Main Outcomes and Measures</h3> Payments for common surgical procedures from private insurers and overall complication and readmission rates at 30, 60, and 90 days. <h3>Results</h3> There were 368 220 pediatric patients who underwent one of the surgical procedures of interest; 220 899 (60.0%) of the patients were male; 118 977 (32.3%) had their procedure at freestanding CH (CH-A), 75 256 (20.4%) at CH attached to an adult hospital (CH-B), and 173 987 (47.3%) at NCH. The mean (SD) payment for all procedures at CH-A was $6533.56 ($6399.97), $5847.50 ($4947.47) at CH-B, and $5034.25 ($4787.07) at NCH. The mean (SD) overall complication rate was 0.004 (0.06) at CH-A, 0.01 (0.07) at CH-B, and 0.003 (0.06) at NCH. Readmission rates at 30, 60, and 90 days were similar across all hospital types. After adjusting for zip code, year, surgery, surgery setting, and observable patient, hospital, and county characteristics, the estimated payments for inpatient common procedures were 39% higher at CH-A than at NCH. Payments for outpatient common procedures were 34% higher at CH-A than at NCH. <h3>Conclusions and Relevance</h3> In this cohort study, children who underwent common surgical procedures had equivalent clinical outcomes at CH and NCH but the procedures were associated with higher payments and, thus, overall lower value care. To ensure delivery of optimal value to patients and payers, more research is needed to evaluate mechanisms to ensure access, decrease costs, and improve value at both CH and NCH.
PB2299: CLINICAL AND LABORATORY CHARACTERISTICS OF CHILDREN WITH INHERITED THROMBOCYTOPENIA IN A SINGLE EGYPTIAN UNIVERSITY HOSPITAL
Authors: Y. El Chazli, N. S. Badawy, R. Abo Elwafa, M. Salama
Journal: HemaSphere (2022)

Background: Inherited thrombocytopenias (IT) are rare bleeding disorders, which cause a deficiency of platelets in early infancy. This group of disorders is sometimes associated with abnormal phenotypes. ITs are being recognized with increasing frequency. The study of IT in children is difficult due to the heterogeneity of the patients and the rarity of each disease. To the best of our knowledge, the study of the epidemiology of such a hematological finding in our area has not been previously published. Aims: To report the clinical and laboratory characteristics of children with inherited thrombocytopenia. Methods: The files of all children with thrombocytopenia followed at the Hematology clinic of Alexandria University Children’s Hospital, Alexandria, Egypt, were retrospectively analysed. Patients who joined the clinic until the 31st of December 2021 were included. IT was considered in patients with suggestive clinical features as young age of presentation, abnormal physical features, positive family history, no response to ITP drugs. The blood film was revised for assesment of platelet size and morphology. Flowcytometry of platelet glycoproteins was perfromed. Results: Forty patients were identified as suspected IT. The median age of patients was 65 months, ranging from 9 months to 17 years at the time of the study. Thrombocytopenia was first discovered at a median age of 20 months. Fifty-five percent were males. In 55% of patients, there was a history of thrombocytopenia in a family member, and 42% had consanguineous parents (first-degree cousins). The most common bleeding symptoms were purpura and ecchymoses, followed by mucosal bleeding. The median platelet count at diagnosis was 30 ×103 cell/uL, while the lowest was 9 ×103 cell/uL. The initial recorded diagnosis was ITP in 65% of patients, followed by Glanzmann thrombasthenia (7.5%), CAMT and WAS (5% each). After revision of the diagnosis, BSS was confirmed in 20% of patients, WAS in 12.5%; some rare disorders were identified like MYH9-RD and Glanzmann thromboasthenia with macrothrombocytopenia. In 35% of patients the diagnosis was not defined yet. Seven patients were missing for further workup, and seven patients were sent for genetic testing. Summary/Conclusion: Inherited thrombocytopenias are rare disorders that are frequently overlooked. A detailed family and disease history, examination of the blood film by an expert, and assessment of the response to usual ITP treatments are all simple methods that help pick up suspected cases. Simple tests like platelet glycoprotein flowcytometry or MYH9 staining can confirm the diagnosis in a substantial number of patients. Genetic tetsing is the final step for undiagnosed cases.
PB2009: OPPORTUNITIES OF THERAPY IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA WITH DIALYSIS-DEPENDENT RENAL IMPAIRMENT
Authors: I. Kliuchagina, A. Semenova, E. Gromova, L. Kuznetsova, O. Kolomeytsev, G. Tumyan, D. Osmanov
Journal: HemaSphere (2022)

Background: Renal impairment (RI) is one of the most frequent complications of multiple myeloma (MM). At the diagnosis time RI is detected in 20-40% of patients, in 2-4% of patients with newly diagnosed MM develop dialysis-dependent RI, which is associated with early mortality and a high complications’ incidence. Aims: Compare PFS and OS in patients with newly diagnosed MM with dialysis-dependent renal impairment depending on the achievement of renal response and autoHSCT. Methods: The study included 39 patients with newly diagnosed MM III B stage (Durie-Salmon) with dialysis-dependent RI for the period from 2000 to 2020. 24 (61.5%) of patients were male, the median age is 58 years (range 36 to 76). The diagnosis was established in accordance with the criteria of IMWG-2014. Cytogenetic examination was performed in 17 (43.6%) patients. 4 (10.2%) patients have high–risk translocation t (4;14). At the disease onset the median creatinine level was 631 mkmol/L (range 448 to 2138), median CKD-EPI was 7 ml/min/1.73 m2 (ranged 2 to 10 ml/min/1.73 m2). The following programs were used as induction therapy: CyBorD - 10 (25.6%), VCP - 6 (15.4%), CP – 14 (35.9%) VAD – 7 (17.9%), VMCP – 2 (5.1%). Bortezomib-containing regimens were received by 16 patients (41%). 30 (77%) patients were the candidates for autoHSCT. AutoHSCT was performed in 8 (20.5%) patients, in 3 (7.7%) cases - tandem autoHSCT. An antitumor response was evaluated after 3-4 courses of induction therapy and on the 100th day after autoHSCT. The results of the study were subjected to statistical processing using the Statistica program (version 10.0). The survival analysis was carried out using the Kaplan–Meier method. Results: 25 patients (64.1%) during induction therapy achieved renal response: complete response - 1 (2.6%) patient, partial response - 10 (25.6%) patients, minimal response -14 (35.9%) patients. 14 (35.9%) patients didn’t have any response. The achievement of any renal response was associated with an improvement 3-year PFS 61.1% (95%CI 43.7, 76.1) vs. 18.9% (95% CI 11.8, 23,9) (p = 0.045), 3-year OS 72.2% (95%CI 58.2, 86,1) vs. 38.1% CI (27.6, 48,2) (p = 0.049) respectively. 3-year PFS in patients who underwent autoHSCT was 48,6% (CI 35.8, 67,2), 3-year OS - 67,2% (CI 46.8, 78.9) to compare with patients who were the candidates for autoHSCT, but didn’t undergo autoHSCT: 3-year PFS 17,9% (CI 9.7, 31,2), 3-year OS – 33,7% (CI 16.7, 57.3) (p=0,036). There wasn’t transplantation related mortality. Summary/Conclusion: Achieving at least a minimal renal response as well as performing autoHSCT improve the PFS and OS in patients with newly diagnosed MM with dialysis-dependent RI.
Biochemical Failure Is Not a Surrogate End Point for Overall Survival in Recurrent Prostate Cancer: Analysis of NRG Oncology/RTOG 9601
Authors: William C. Jackson, Ming Tang, Matthew J. Schipper, Howard M. Sandler, Zachary S. Zumsteg, Jason A. Efstathiou, William U. Shipley, Wendy Seiferheld, Himanshu R. Lukka, Jean-Paul Bahary, Anthony L. Zietman, Thomas M. Pisansky, Kenneth L. Zeitzer, William A. Hall, Robert T. Dess, Richard D. Lovett, Alexander G. Balogh, Felix Y. Feng, Daniel E. Spratt
Journal: Journal of Clinical Oncology (2022)

Metastasis-free survival (MFS), but not event-free survival, is a validated surrogate end point for overall survival (OS) in men treated for localized prostate cancer. It remains unknown if this holds true in biochemically recurrent disease after radical prostatectomy. Leveraging NRG/RTOG 9601, we aimed to determine the performance of intermediate clinical end points (ICEs) as surrogate end points for OS in recurrent prostate cancer.NRG/RTOG 9601 randomly assigned 760 men with recurrence after prostatectomy to salvage radiation therapy with 2 years of placebo versus bicalutamide 150 mg daily. ICEs assessed were biochemical failure (BF) per NRG/RTOG 9601 (prostate-specific antigen nadir + 0.3-0.5 ng/mL or initiation of salvage hormone therapy; [BF1]) and NRG/RTOG 0534 (prostate-specific antigen nadir+2 ng/mL; [BF2]), distant metastasis (DM), and MFS (DM or death). Surrogacy was assessed by the Prentice criteria and a two-stage meta-analytic approach (condition one assessed at the patient level with Kendall's τ and condition two assessed by randomly dividing the entire trial cohort into 10 pseudo trial centers and calculating the average R2 between treatment hazard ratios for ICE and OS).BF1, BF2, DM, and MFS satisfied the four Prentice criteria. However, with the two-condition meta-analytic approach, there was strong correlation between MFS and OS (τ = 0.86), moderate correlation between DM and OS (τ = 0.66), and weaker correlation between BF1 (τ = 0.25) or BF2 (τ = 0.40) and OS. Similarly, for condition two, the treatment effect of antiandrogen therapy on MFS and OS were correlated (R2 = 0.67), but this was not true for BF1 (R2 = 0.09), BF2 (R2 = 0.12), or DM (R2 = 0.18) and OS.MFS is also a strong surrogate for OS in men receiving salvage radiation therapy for recurrence after prostatectomy. Caution should be used when inferring survival benefit from effects on BF in biochemically recurrent prostate cancer. Lack of comorbidity data did not allow us to assess whether BF in men with no/minimal comorbidity could serve as a surrogate for OS.
P1348: COMPARISON OF NATURAL KILLER CELL RECONSTITUTION AFTER HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION DEPENDING ON THE VARIANT OF T-CELL DEPLETION
Authors: Z. Konova, I. Galtseva, N. Kapranov, J. Davydova, M. Drokov, M. Dovidenko, N. Popova, A. Dmitrova, U. Maslikova, O. Starikova, E. Mikhaltsova, O. Koroleva, D. Dubnyak, E. Kolgaeva, F. Omarova, V. Vasilyeva, L. Kuzmina, E. Parovichnikova
Journal: HemaSphere (2022)

Background: Natural killer cells (NK) can play a decisive role in preventing early relapses and infectious complications after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) due to their comparatively fast reconstitution after HSCT. And when performing haplo-HSCT with depletion of TCRαβ-positive T-lymphocytes, the graft versus leukemia (GVL) effect is carried out only at the expense of donor NK cells. NK differentiate from immature (CD56bright) to mature (CD56dim) and terminally differentiated. NK differentiation to the subpopulation CD56dimCD16+ is necessary to implement an alloreactive NK cell immune response. Aims: To study the rate and features of NK cell reconstitution after haplo-HSCT. Methods: The study included 16 patients with acute myeloid leukemia (AML) and 13 patients with acute lymphoblastic leukemia (ALL) who underwent haplo-HSCT at the National Medical Research Center for Hematology from April 2020 to June 2021. 15 patients - with the use of post-transplant cyclophosphamide (PT-Cy), 14 - with previous TCRαβ-depletion. To assess the reconstitution of NK, all patients underwent immunophenotypic studies of peripheral blood samples at +14, +30, +60, +90 and +180 days after haplo-HSCT using a 12-color flow cytometer (CytoFlex Beckman Coulter, USA). Monoclonal antibodies to human differentiation antigens CD3, CD8, CD158a, CD158b, CD158e, CD159a, CD57, CD16, CD56, CD14, CD45, CD62L were used in the analysis of subpopulations of NK cells. The SAS 9.4 software (Sas institute inc., Cary, NC, USA) was used for statistical data processing. Differences were considered statistically significant at p<0.05. Results: NK reached a mature immunophenotype faster in the case of haplo-HSCT with TCRαβ-depletion: by day +30 after HSCT, the median proportion of CD56dimCD16+ NK cells with TCRαβ-depletion was 57% versus 9% when using PT-Cy, p= 0.0045. Significant differences persisted up to +60 (74% vs. 41% (p=0.0079)) and +90 days after haplo-HSCT (81% vs. 46% (p=0.0076)) (Fig. 1). Image:Summary/Conclusion: The rate of reconstitution and the acquisition of an alloreactive phenotype by NK depends on the variant of T-cell depletion; faster recovery occurs when performing haplo-HSCT with TCRαβ-depletion. When using PT-Cy, the recovery of the mature NK cell population occurs at a later time after haplo-HSCT (from +3 to + 6 months) and such patients may benefit from transfusions of donor NK cells at the post-transplant stage. This approach can be considered as a worthy alternative to donor.
PB1959: ESTABLISHMENT OF A NEW MULTIPLE MYELOMA (MM) RESEARCH MODEL USING MAGNETICALLY EMPOWERED TUMOR CELLS AND NK CELLS
Authors: Z. Wang, R. Hou, L. Tan, J. Zhang, D. Zhang, D. Pan, Q. Chen, L. Tang, Y. Hu, X. Kong, Q. Jiang
Journal: HemaSphere (2022)

Background: Multiple myeloma (MM) is different from leukemia on pathogenesis, clinical features, and treatment prognosis, it remains a type of incurable cancer although there are such treatment as hematopoietic stem cell transplantation and CAR-T, etc. One of the important characteristics is that MM cells are focally distributed within the bone marrow. Aims: In order to mimic the clinical characteristics of local distribution of MM cells, we try to establish such in vitro and in vivo model by the technology of magnetically empowered tumor cells (MET) and magnetically empowered NK cells (MENK). Methods: 1) Myeloma cells (NCI-H929) labeled with green fluorescent protein (GFP) and luciferase (Luc) dual reporter genes were constructed. 2) To simulate the MM situation with an in vitro model, the magnetically GFP+Luc+NCI-H929 was inoculated as MET into 6-well plate, cell islands were formulated under according tiny magnetisms, then MENK was added to observe its treatment effect. 3) By injecting the magnetically GFP+Luc+NCI-H929 as MET into the right femur under a special-made magnetism, the in vivo nude mouse tumor model was established. Then the MENK was added to kill the tumor formed within the femur. The efficacy was evaluated by X-ray (or micro-CT), monoclonal protein, as well as morphology, immunology, cytogenetics and molecular biology (MICM) analysis. 4) To explore the possibility of establishing other kinds of MET tumor models. Results: 1) We established the in vitro model with locally distributed MET, and the MENK can efficiently eliminate the MM cells. 2) GFP+Luc+NCI-H929 specifically located in the femur in nude mouse model, the model was a quite successful and ideal in vivo model for MM study since it has cluster of MM cells in injected femur and localized bone destruction. 3) Other different kinds of tumor models were successfully established. It illustrated that MET technology can be applied on multiple kinds of tumor cells. Image:Summary/Conclusion: We established the in vivo and in vitro models for MM with the technology of MET/MENK which can be used not only for mechanism research but also for the therapy evaluation, such as CAR-NK and CAR-T.
Mesenchymal Stem Cell Exosomes Encapsulated Oral Microcapsules for Acute Colitis Treatment
Authors: Jingjing Gan, Lingyu Sun, Guopu Chen, Wenjuan Ma, Yuanjin Zhao, Lingyun Sun
Journal: Advanced Healthcare Materials (2022)

Abstract Mesenchymal stem cells derived exosomes (MSC‐exos) exhibit an intrinsic and directed efficiency for multiple diseases, while their versatile and effective delivery to the target site is still a challenge. Herein, inspired by the acids and enzymes resistant property of sealing gelatin capsules, novel MSC‐exo‐encapsulated oral microcapsules are presented for colitis treatment. Based on a microfluidic electrospray technique, MSC‐exos are first encapsulated in sodium alginate (SA) hydrogel microspheres with sustainable bioactivity. The resultant SA microspheres are then coated with a middle gelatin layer to protect MSC‐exos from degradation. Especially, with an enteric coating‐Eudragit FS30D on the outer layer, the resistance of the microcapsules in gastric juice is further enhanced. The prepared microcapsules maintain the stability and bioactivity of the MSC‐exos during storage, protect them from the harsh conditions in the gastrointestinal tract, and enable the release of actives in the suitable sites for exerting their biological functions. In addition, these MSC‐exos encapsulated microcapsules reduce the proinflammatory cytokines levels of inflammatory macrophages and impaired colonic epithelial cells, which exhibit superior damage repair ability in injured colon sites. Thus, it is believed that the proposed oral MSC‐exos encapsulated microcapsules are valuable for many practically clinical treatments.